The multifaceted aims of this ongoing research project include: 1) to further analyze the profile of activity exhibited by select narcotic agonists administered to young rats at crucial stages of CNS development; 2) to examine the importance of the period of CNS development per se as a determinant of the ability of narcotic agonists to produce alterations in behavior, neurochemical transmitter systems in the brain and pharmacological responsivity later in life, as well as the qualitative nature of the changes produced, their extent and relative persistence; 3) to investigate the consequences of neurochemical changes produced by fairly specific neurohumoral modulators and possible similarities to those associated with narcotics; 4) to study the possible role of certain biogenic amines in the actions of narcotics at a mechanistic level by examining the effects of interference with the coordinated development of serotonergic, noradrenergic and dopaminergic systems in the young rat and its potential relationship to alterations in behavior, neurochemical maturation and/or changes in the responsivity to narcotics. Narcotic agonists, primarily methadone and 1-alpha-acetylmethadol, and certain fairly specific neurohumoral modulators will be studied alone and in combination. A series of sequential procedures, previously developed in the course of this project, will be used to longitudinally assess certain measures of overall viability, and general, neuromotor, and behavioral maturation of control and drug-treated animals from birth to relative adulthood. These will be employed to facilitate identifying nonspecific toxic effects which could occur and produce neurochemical changes unrelated to mechanisms presumably subserving the effects under investigation.